We have determined the incidence with which the t(14;18) chromosomal translocation involves each of the known DNA breakpoint clusters of the bc1-2 gene in a series of 85 cases of follicular lymphomas. Four breakpoint clusters were identified and the location of the breakpoint may influence the course of disease. Despite t(14;18) translocation, a substantial group (15%) was identified which did not rearrange bc1-2 loci in any of these breakpoint regions, indicating that additional breakpoints remain. We are attempting to clone the DNA sequences at new breakpoint regions and link them to the bc1-2 transcriptional unit. The recently discovered gene encoding the delta chain of the second human T cell receptor lies within an actively rearranging region of the T cell receptor alpha locus. Using DNA probes of this region, we have identified T-delta gene rearrangement as a frequent, early event in precursor T-cell neoplasms (ALL). Prior to our analysis, only one delta variable (V) gene was known. In the course of our study, we have discovered two new productive V- delta genes and together the three V genes may comprise the entire delta V repertoire. In an attempt to identify DNA sequences at the site of chromosomal translocation in Hodgkin's disease, we have cloned and sequenced the rearranged genomic DNA region of both the immunoglobulin heavy chain gene and T cell receptor beta chain gene in the Hodgkin's disease cell line, L428. The rearranged VH gene we cloned from L428 is a member of the recently discovered VH-V family reported as frequently rearranged in B cell neoplasms. However, we find VH- V either germline or deleted, but only rarely rearranged, in B cell ALL, CLL and follicular lymphoma.